FDA sets out evidentiary expectations for 510(k) Implant Devices
The Food and Drug Administration has issued draft guidance detailing its expectations for all 510(k) implant devices[i]. This includes considerations regarding the indications for use, the intended duration of implantation, non-clinical testing, human factors and usability testing, clinical performance testing, patient experience information (where relevant), and labeling.
For a new device to be Substantially Equivalent (SE) to a predicate device it must meet specific criteria. First it must have the same intended use. It must have the same technological characteristics or, if different, then the technological characteristic differences of the new device must not raise different safety and effectiveness questions. And the new device must be as safe and effective as the predicate device.
Given the scientific and clinical considerations that implants often raise, the FDA expects a variety of non-clinical and/or clinical data to demonstrate the new implant meets those equivalent safe and effective criteria.
The type and quantity of performance data required to support substantial equivalence will vary depending on the device, device type, and the differences identified between the new device and the predicate device. However, the new draft guidance covers considerations that are applicable to all implant types that are subject to the 510(k) requirements.
General Considerations
There are some fundamental considerations that the guidance raises.
First, manufacturers must consider the indications for use of the proposed device. Submitters – defined in the guidance as the entity that submits the 510(k) for review — need to carefully consider the indications for use of the device. This includes the specific intended patient population, disease state, and conditions of use, when designing or conducting the performance testing. The performance data provided should be representative of the way in which the device is indicated to be used, including the anatomical location(s) for which it is indicated. As noted in the guidance, while orthopedic and dental devices may both interface with bone, both the biochemical and the biomechanical environment will differ, making data generated for one type not applicable for the other type.
A second key consideration is the intended duration of implantation, which submitters should consider when designing or conducting performance testing. This duration may change the performance testing used, although the FDA’s least burdensome provisions (laid out in final guidance published in February 2019) may allow results from shorter duration testing to be extrapolated to provide information on long-term performance[ii].
A third consideration is the anticipated patient and physician experience with the implant. Submitters should consider whether certain features could increase risks when compared to the predicate. These include risks associated with:
- Everyday activities, such as how airport screening might affect the implant
- Ongoing or future medical care
- Reoperation or revision associated with the implant
- Variations between different patient populations
- Duration of use that might result in discomfort or other adverse events
- User interaction with the implant, including user training and instructions for maintaining the device
- Device design/ergonomics and human factors related to use by a physician
- Implantation procedure, such as operating time, infection, tissue damage, etc.
Non-Clinical Recommendations
It may not be required to provide all the information or performance testing for non-clinical issues, but it is recommended to provide justification as to why it is not applicable to the 510(k) submission. The FDA has linked further guidance on each of these considerations. For example, for biocompatibility, FDA has published the “Use of International Standard ISO 10993-1[iii], ‘Biological evaluation of medical devices – Part 1: Evaluation and testing within a risk management process[iv],” which generally aligns with ISO 10993-1 with a few modifications. For sterility, the agency has published the guidance document “Submission and Review of Sterility Information in Premarket Notification (510(k)) Submissions for Devices Labeled as Sterile[v]”. Other non-clinical considerations that have associated guidance documents include:
- Shelf Life and Packaging
- Reprocessing and Cleaning
- Software and Cybersecurity
- Electrical Safety and Electromagnetic Compatibility
- Magnetic Resonance (MR) Compatibility
- Other Non-Clinical Performance Testing (such as testing for corrosion, fatigue, degradation, etc.)
- Animal Testing
- Implant Device Design Considerations
Human Factors/Usability
Human factor information may need to be presented to demonstrate SE for certain 510(k) implant devices. The reason for that is so the differences between the user interface of the predicate device and the new device can be evaluated to determine its impact on safety and effectiveness.
Clinical Performance Testing
Clinical performance testing may be required in certain scenarios as outlined in another recent 510(k) guidance, Recommendations for the Use of Clinical Data in Premarket Notification [510(k)] Submissions[vi].
Patient Experience Information
The FDA promotes the collection, analysis, and integration of patient experience data for implants. This includes patient preference information (PPI) and patient-reported outcomes, which have associated FDA guidance documents “Patient-Reported Outcome Measures: Use in Medical Product Development to Support Labeling Claims[vii]” and “Principles for Selecting, Developing, Modifying, and Adapting Patient-Reported Outcome Instruments for Use in Medical Device Evaluation[viii].”
Labeling and Other Recommendations
To satisfy the requirements of 21 CFR 807.87(e)[ix], a 510(k) must contain proposed labels, labeling, and advertisement material that sufficiently describes the device, its intended use, and the directions for use. Additionally, since implants are intended to remain in the patient, the FDA expects that the manufacturer will provide appropriate information to the practitioner, who in turn will provide it to the patient. That includes information about the implantation procedure and the risks and benefits post-implantation. This information is usually in the form of instructions for use, implant cards, and other patient information leaflets, which address associated risks.
Preparing for 510(k) submissions
The FDA continues to provide detailed guidance for companies developing Class II devices which required a 510(k), with the objective of assisting submitters while ensuring patient safeguards. Are you preparing to submit a 510(k) premarket notification to the agency? Are you struggling to demonstrate equivalency and gather the required data? Have you experienced issues with your submission? We would be interested in hearing from you.
About the author: John Lockwood is Senior Director, US Head of Medical Devices and IVDs, Cencora PharmaLex. John has over 25 years of experience in quality, regulatory, operations, and development roles in the life sciences industry, including industry experience at Abbott Laboratories and Roche Diagnostics. He holds professional certifications from RAPS and ASQ and has a Bachelor of Science in Chemistry from the University of Illinois.
[i] Evidentiary Expectations for 510(k) Implant Devices, Draft Guidance, FDA. https://www.fda.gov/media/171835/download
[ii] The Least Burdensome Provisions: Concept and Principles, FDA, Feb 2019. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/least-burdensome-provisions-conceptand-principles
[iii] ISO 10993-1:2018. Biological evaluation of medical devices. https://www.iso.org/standard/68936.html
[iv] Biological evaluation of medical devices – Part 1: Evaluation and testing within a risk management process, FDA. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/use-international-standard-iso-10993-1-biological-evaluation-medical-devices-part-1-evaluation-and
[v] Submission and Review of Sterility Information in Premarket Notification (510(k)) Submissions for Devices Labeled as Sterile, FDA. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/submission-and-review-sterility-information-premarket-notification-510k-submissions-devices-labeled
[vi] Recommendations for the Use of Clinical Data in Premarket Notification [510(k)] Submissions, FDA. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/recommendations-use-clinical-data-premarket-notification-510k-submissions
[vii] Patient-Reported Outcome Measures: Use in Medical Product Development to Support Labeling Claims, FDA. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/patient-reported-outcome-measures-use-medical-product-development-support-labeling-claims
[viii] Principles for Selecting, Developing, Modifying, and Adapting Patient-Reported Outcome Instruments for Use in Medical Device Evaluation, FDA. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/principles-selecting-developing-modifying-and-adapting-patient-reported-outcome-instruments-use
[ix] Code of Federal Regulations, 21 CFR 807.87(e). https://www.ecfr.gov/current/title-21/chapter-I/subchapter-H/part-807/subpart-E/section-807.87
